This is a proposal to establish a program-project directed to the comprehensive understanding of the basic derangements of cell function which lead to mental retardation in children. The underlying approach is the application of biochemical techniques to delineate the abnormalities responsible for retardation syndromes associated with inherited metabolic diseases by investigation of model systems ranging from patients and intact animals to isolated cells and subcellular systems. Emphasis will be placed on growth and development as important factors. The program project is composed of nine individual research projects each to be directed by an experienced researcher. These include: 1) Studies of perinatal brain toxicity in the rat. 2) Myelination in chick embryos. 3) Development and regulation of brain lysosomal enzymes. 4) Regulation of galactose metabolism in perfused liver. 5) Neuronal cells in tissue culture as model systems for brain dysfunction. 6) Biochemical abnormalities of galactosemic human fibroblasts. 7) Regulation of protein synthesis and degradation in cultured human cells with genetic abnormalities. 8) The basis of mental retardation in human cystinuria and 9) The etiology of hypoglycemia in infants and children.